Abstract: bs_bs_banner doi:10.1111/jgh.15796 CLINICAL TRIAL Gut microbiota-derived synbiotic formula (SIM01) as a novel adjuvant therapy for COVID-19: An open-label pilot study Lin Zhang,*,†,‡1 Zhilu Xu,*,†,‡1 Joyce W Y Mak,*,†,‡ Kai Ming Chow,† Grace Lui,†,§ Timothy C M Li,† ¶ † Chun Kwok Wong, Paul K S Chan,** Jessica Y L Ching, Yasuhiro Fujiwara,†† Francis K L Chan*,†,‡ and ,†,‡ Siew C Ng* *Microbiota I-Center (MagIC), †Department of Medicine and Therapeutics, Faculty of Medicine, ‡State Key Laboratory of Digestive Disease, Institute of Digestive Disease, Li Ka Shing Institute of Health Sciences, Faculty of Medicine, §Stanley Ho Centre for Emerging Infectious Diseases, Faculty of Medicine, ¶ Department of Chemical Pathology, Faculty of Medicine, **Department of Microbiology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China; and ††Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan Key words immunity, microbiota, probiotics, SARS-CoV-2. Accepted for publication 3 February 2022. Correspondence Siew C Ng and Francis K L Chan, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China. Email: siewchienng@cuhk.edu.hk; fklchan@cuhk.edu.hk Declaration of conflict of interest: Prof. Siew Ng and Prof. Francis Chan report serving as founder member for GenieBiome Limited. Prof. Siew Ng also has served as advisory board member for Pfizer, Ferring, Janssen, Abbvie and speaker for Ferring, Tillotts, Menarini, Janssen, Abbvie, and Takeda. She has received research grants from Olympus, Ferring and Abbvie. Prof. Francis Chan has served as the Director & Board member of CUHK Medical Centre Limited and First Director of the Board of Directors for CUHK Multi-Scale Medical Robotics Centre Limited. He also has served as advisor and lecture speaker for Eisai Co. Ltd, AstraZeneca, Pifzer Inc, Takeda Pharmaceutical Co., Takeda (China) Holdings Co. Ltd. Prof. Siew Ng, Prof. Francis Chan, and Dr Zhilu Xu are inventors of patent applications for “Composition for Improving Immunity” (CN202010657312.5, CN202011259564.9, CN202110223880.9, PCT/CN2021/090531, and TW110115155). Prof. Siew Ng and Prof. Francis Chan are inventors of patent applications for Abstract Background and Aim: Gut dysbiosis is associated with immune dysfunction and severity of COVID-19. Whether targeting dysbiosis will improve outcomes of COVID-19 is unknown. This study aimed to assess the effects of a novel gut microbiota-derived synbiotic formula (SIM01) as an adjuvant therapy on immunological responses and changes in gut microbiota of hospitalized COVID-19 patients. Methods: This was an open-label, proof-of-concept study. Consecutive COVID-19 patients admitted to an infectious disease referral center in Hong Kong were given a novel formula of Bifidobacteria strains, galactooligosaccharides, xylooligosaccharide, and resistant dextrin (SIM01). The latter was derived from metagenomic databases of COVID-19 patients and healthy population. COVID-19 patients who were admitted under another independent infectious disease team during the same period without receiving SIM01 acted as controls. All patients received standard treatments for COVID-19 according to the hospital protocol. We assessed antibody response, plasma proinflammatory markers, nasopharyngeal SARS-CoV-2 viral load, and fecal microbiota profile from admission up to week 5. Results: Twenty-five consecutive COVID-19 patients received..